The effects of particle size on measurement of airway hyperresponsiveness to methacholine

Ann Allergy Asthma Immunol. 2013 May;110(5):359-63. doi: 10.1016/j.anai.2013.02.014. Epub 2013 Mar 19.


Background: The effect of particle size on methacholine provocation concentration causing a decrease in forced expiratory volume of 1 second (FEV1) of 20% (PC20) is debatable.

Objective: To evaluate the functional effects of 3 different particle size nebulizers on methacholine PC20.

Methods: Participants were randomly assigned to have 3 methacholine challenges on 3 separate days. Nebulizer mass median aerodynamic diameter (MMAD) was provided by manufacturers. The Wright nebulizer (MMAD, 1.0 μm), Aeroneb (MMAD, 3 μm), and Aeroneb (MMAD, 5 μm) were calibrated, and the nebulizer outputs were calculated to administer 0.26 mL of methacholine over 120, 112, and 83 seconds, respectively. After each inhalation, spirometry was performed and the test was terminated when the PC20 was achieved.

Results: Eight nonsmoking patients with mild asthma (4 male and 4 female) completed the study. The mean (SD) age was 25 (13.9) years, and the mean (SD) baseline FEV1 was 88% (11.3%). Patients using the Aeroneb (MMAD, 5 μm) nebulizer had the lowest PC20 (bronchoconstricted at lowest methacholine concentration), with a PC20 geometric mean of 0.62 mg/mL compared with patients using the Aeroneb (MMAD, 3.0 μm), who had a PC20 of 1.76 mg/mL, and patients using the Wright nebulizer (MMAD, 1.0 μm), who had a PC20 of 6.32 mg/mL. There was a significant difference in PC20 across all particle sizes (P < .001). The pairwise differences revealed a P < .001 between 3 μm and 1 μm and between 5 μm and 1 μm and a P = .008 between 5 μm and 3 μm.

Conclusion: Our results reveal a variability in methacholine PC20 using 3 different nebulizers, despite adjusting the nebulizers' outputs. Our results are consistent with the previous reports, which recommended using larger particle size nebulizers in the assessment of airway hyperresponsiveness in asthma.

Trial registration: Identifier: NCT00529477.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / diagnosis*
  • Bronchial Hyperreactivity / physiopathology
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents / administration & dosage
  • Bronchoconstrictor Agents / chemistry*
  • Cross-Over Studies
  • Female
  • Humans
  • Male
  • Methacholine Chloride / administration & dosage
  • Methacholine Chloride / chemistry*
  • Middle Aged
  • Particle Size
  • Spirometry
  • Young Adult


  • Bronchoconstrictor Agents
  • Methacholine Chloride

Associated data